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Platelet Analysis in the Thrombus Plus Serum BNP for Detecting Clot-Related Atrial Fibrillation. Results From the ITACAT Multicentric Registry

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Abstract

Occult atrial fibrillation (AF) is a common cause of cryptogenic stroke. This study aimed to investigate the utility of surrogate markers within the clot (clot markers), in combination with serum biomarkers, to identify AF-associated clots in patients who underwent mechanical thrombectomy. Each retrieved thrombus was analyzed to identify fibrin, red blood cells, platelets — CD61 staining (PLT) and T-CD4 lymphocyte/macrophage/monocyte (CD4) profile. Serum biomarkers such as D-dimer, lipoprotein (A), and brain natriuretic peptide (BNP) were also assessed in the acute phase of the stroke. Patients with stroke-related AF and large artery atherosclerosis (LAA) stroke were compared by matched case-control design to identify markers associated with AF clot profile. The predictive abilities of clot markers and serum biomarkers to detect AF clot were tested in patients with cryptogenic stroke. In patients with AF clot, the PLT percentage was higher (66.64% vs. 55.43%, OR = 1.03); CD4 percentage was lower (3.84% vs. 7.95%, OR = 0.95); and BNP marker was higher (2114 pg/ml vs. 276 pg/ml, OR = 1.04) compared to LAA clot. PLT was independently associated to AF-clot (OR, 1.04) but demonstrated moderate ability to identify AF-clot cases (C-test 0.668, p = 0.018). The combination of PLT with BNP significantly improved AF-clot prediction (C-test 0.847, p < 0.001). The clot composition of patients with cryptogenic stroke and AF detection showed four-fold higher PLT and BNP pattern of risk than patients with cryptogenic stroke without AF detection (38.5% vs. 8.7%) (OR = 1.40). Integrating intra-thrombus platelet with serum BNP offers a promising approach for detecting AF-associated clots in patients with cryptogenic stroke.

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Data Availability

The data that support the findings of this study are available on request from the corresponding author.

References

  1. Hart RG, Diener HC, Connolly SJ. Embolic strokes of undetermined source: support for a new clinical construct--authors’ reply. Lancet Neurol. 2014;13(10):967.

    Article  PubMed  Google Scholar 

  2. Ntaios G, Hart RG. Embolic stroke. Circulation. 2017;136(25):2403–5.

    Article  PubMed  Google Scholar 

  3. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723–31.

    Article  PubMed  Google Scholar 

  4. Gawaz M, Stellos K, Langer HF. Platelets modulate atherogenesis and progression of atherosclerotic plaques via interaction with progenitor and dendritic cells. J Thromb Haemost. 2008;6(2):235–42.

    Article  CAS  PubMed  Google Scholar 

  5. Buxhofer-Ausch V, Steurer M, Sormann S, Schloegl E, Schimetta W, Gisslinger B, et al. Influence of platelet and white blood cell counts on major thrombosis - analysis from a patient registry in essential thrombocythemia. Eur J Haematol. 2016;97(6):511–6.

    Article  CAS  PubMed  Google Scholar 

  6. Boeckh-Behrens T, Kleine JF, Zimmer C, Neff F, Scheipl F, Pelisek J, et al. Thrombus histology suggests cardioembolic cause in cryptogenic stroke. Stroke. 2016;47(7):1864–71.

    Article  CAS  PubMed  Google Scholar 

  7. Swystun LL, Liaw PC. The role of leukocytes in thrombosis. Blood. 2016;128(6):753–62.

    Article  CAS  PubMed  Google Scholar 

  8. Staessens S, De Meyer SF. Thrombus heterogeneity in ischemic stroke. Platelets. 2021;32(3):331–9.

    Article  CAS  PubMed  Google Scholar 

  9. Schuhmann MK, Gunreben I, Kleinschnitz C, Kraft P. Immunohistochemical analysis of cerebral thrombi retrieved by mechanical thrombectomy from patients with acute ischemic stroke. Int J Mol Sci. 2016;17(3):298.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Dargazanli C, Rigau V, Eker O, Riquelme Bareiro C, Machi P, Gascou G, et al. High CD3+ cells in intracranial thrombi represent a biomarker of atherothrombotic stroke. PLoS One. 2016;11(5):e0154945.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Blair P, Rex S, Vitseva O, Beaulieu L, Tanriverdi K, Chakrabarti S, et al. Stimulation of Toll-like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3-kinase. Circ Res. 2009;104(3):346–54.

    Article  CAS  PubMed  Google Scholar 

  12. Grosse GM, Werlein C, Blume N, Abu-Fares O, Götz F, Gabriel MM, et al. Circulating cytokines and growth factors in acute cerebral large vessel occlusion-association with success of endovascular treatment. Thromb Haemost. 2022;122(4):623–32.

    Article  PubMed  Google Scholar 

  13. Ramos-Pachón A, López-Cancio E, Bustamante A, Pérez de la Ossa N, Millán M, Hernández-Pérez M, et al. D-Dimer as predictor of large vessel occlusion in acute ischemic stroke. Stroke. 2021;52(3):852–8.

    Article  PubMed  Google Scholar 

  14. Maruyama K, Shiga T, Iijima M, Moriya S, Mizuno S, Toi S, et al. Brain natriuretic peptide in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2014;23(5):967–72.

    Article  PubMed  Google Scholar 

  15. Cao R, Jiang Y, Li L, Lu Y, Wang J, Yu K, et al. BNP on admission combined with imaging markers of multimodal CT to predict the risk of cardioembolic stroke. Dis Markers. 2022;2022:3327967.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Pagola J, Juega J, Francisco-Pascual J, Bustamante A, Penalba A, Pala E, et al. Predicting atrial fibrillation with high risk of embolization with atrial strain and NT-proBNP. Transl Stroke Res. 2021;12(5):735–41.

    Article  CAS  PubMed  Google Scholar 

  17. Anderson A, Klein J, White B, Bourgeois M, Leonard A, Pacino A, et al. Training and certifying users of the National Institutes of Health Stroke Scale. Stroke. 2020;51(3):990–3.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344–418.

    Article  PubMed  Google Scholar 

  19. Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41.

    Article  PubMed  Google Scholar 

  20. Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology. 1983;148(3):839–43.

    Article  CAS  PubMed  Google Scholar 

  21. Brinjikji W, Nogueira RG, Kvamme P, Layton KF, Delgado Almandoz JE, Hanel RA, et al. Association between clot composition and stroke origin in mechanical thrombectomy patients: analysis of the Stroke Thromboembolism Registry of Imaging and Pathology. J Neurointerv Surg. 2021;13(7):594–8.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kitano T, Hori Y, Okazaki S, Shimada Y, Iwamoto T, Kanki H, et al. An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Thromb Haemost. 2022;122(3):415–26.

    Article  PubMed  Google Scholar 

  23. García-Tornel Á, Rubiera M, Requena M, Muchada M, Pagola J, Rodriguez-Luna D, et al. Sudden recanalization: a game-changing factor in endovascular treatment of large vessel occlusion strokes. Stroke. 2020;51(4):1313–6.

    Article  PubMed  Google Scholar 

  24. Pagola J, Juega J, Francisco-Pascual J, Moya A, Sanchis M, Bustamante A, et al. Yield of atrial fibrillation detection with textile wearable holter from the acute phase of stroke: Pilot study of Crypto-AF registry. Int J Cardiol. 2018;251:45–50.

    Article  PubMed  Google Scholar 

  25. Lee S, Bartlett B, Dwivedi G. Adaptive immune responses in human atherosclerosis. Int J Mol Sci. 2020;21(23)

  26. Dossena M, Ferrario A, Lopardo V, Ciaglia E, Puca AA. New Insights for BPIFB4 in Cardiovascular Therapy. Int J Mol Sci. 2020;21(19):7163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Juega J, Palacio-Garcia C, Rodriguez M, Deck M, Rodriguez-Luna D, Requena M, et al. ITACAT study group. Monocyte-to-Lymphocyte Ratio in Clot Analysis as a Marker of Cardioembolic Stroke Etiology. Transl Stroke Res. 2022;13(6):949–958.

  28. Sporns PB, Hanning U, Schwindt W, Velasco A, Minnerup J, Zoubi T, et al. Ischemic stroke: what does the histological composition tell us about the origin of the thrombus? Stroke. 2017;48(8):2206–10.

    Article  PubMed  Google Scholar 

  29. Fitzgerald S, Dai D, Wang S, Douglas A, Kadirvel R, Layton KF, et al. Platelet-rich emboli in cerebral large vessel occlusion are associated with a large artery atherosclerosis source. Stroke. 2019;50(7):1907–10.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004;350(7):655–63.

    Article  CAS  PubMed  Google Scholar 

  31. Waldo SW, Beede J, Isakson S, Villard-Saussine S, Fareh J, Clopton P, et al. Pro-B-type natriuretic peptide levels in acute decompensated heart failure. J Am Coll Cardiol. 2008;51(19):1874–82.

    Article  CAS  PubMed  Google Scholar 

  32. Sabatine MS, Morrow DA, de Lemos JA, Omland T, Desai MY, Tanasijevic M, et al. Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia. J Am Coll Cardiol. 2004;44(10):1988–95.

    Article  CAS  PubMed  Google Scholar 

  33. Takase H, Dohi Y, Sonoda H, Kimura G. Prediction of atrial fibrillation by B-type natriuretic peptide. J Atr Fibrillation. 2013;5(6):674.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

All the members of the stroke units are acknowledged for their support in the study.

Code Availability

Not applicable.

Funding

This work was supported by “Project 355/C/2017, Fundació La Marató de TV3 in Strokes and traumatic spinal cord and brain injury, 2017 call of projects.”

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Author notes

  1. Jorge Pagola and Jesus Juega equally contributed as first authors.

Authors and Affiliations

  1. Stroke Unit, Department of Neurology, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Autonomous University of Barcelona, Medicine Department, Passeig de la Vall d’Hebron, 119-129, 08035, Barcelona, Spain

    Jorge Pagola, Jesus Juega, Carlos Lazaro, Alvaro Garcia-Tornel, Marta Olive, Manuel Requena, Marta Rubiera, Marian Muchada, Noelia Rodriguez-Villatoro, David Rodriguez-Luna, Marc Ribo & Carlos Molina

  2. Stroke Unit, Department of Neurology, Germans Trias i Pujol University Hospital, Badalona, Spain

    Laura Dorado & Maria Hernandez-Perez

  3. Stroke Unit Department of Neurology Bellvitge University Hospital, Hospitalet de Llobregat, Barcelona, Spain

    Helena Quesada

  4. Department of Neuroradiology, Vall d’Hebron University Hospital, Barcelona, Spain

    David Hernandez, Carlos Piñana & Alejandro Tomasello

  5. Proteomics Unit, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain

    Carolina de-la-Torre

  6. Department of Pathology Vall d’Hebron University Hospital, Barcelona, Spain

    Jessica Camacho & Santiago Ramon-y-Cajal

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  1. Jorge Pagola
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On behalf of ITACAT Study Group

Corresponding author

Correspondence to Jorge Pagola.

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The study was approved by the Ethical Committee in line with the last Helsinki guidelines.

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Pagola, J., Juega, J., Dorado, L. et al. Platelet Analysis in the Thrombus Plus Serum BNP for Detecting Clot-Related Atrial Fibrillation. Results From the ITACAT Multicentric Registry. Transl. Stroke Res. (2023). https://doi.org/10.1007/s12975-023-01220-x

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